A phase I study to evaluate the safety, tolerability, and pharmacokinetics of MSB0254 in Chinese patients with solid tumors.
Authors: Tianshu Liu, Yulong Zheng, Yi Feng, Yiyi Yu, Wei Li, Cheng Xiao, Jiong Qian, Chenyu Mao, Ning Li, Michael Shi, Chuan Qi, LEI Chen, Steven Yu, Jenny Yao, Lingmin Lu, Jianming Wang
Journal: Journal of Clinical Oncology (2022)

3023 Background: MSB0254 is a humanized vascular endothelial growth factor receptor 2 (VEGFR-2) monoclonal antibody. MSB0254 inhibits angiogenesis induced by either VEGF-A or –C. This trial is a phase I study to evaluate MSB0254’s safety, tolerability and PK profiles, as well as early anti-cancer activities in Chinese patients with advanced solid tumors. Methods: In this phase I study (NCT04381325), locally advanced or metastatic solid tumor patients failed previous standard treatments were enrolled. In the dose escalation phase, following 3+3 rules, MSB0254 was given intravenously Q2W (every 2 weeks) at 4mg/kg, 8mg/kg, 12mg/kg, 16mg/kg, and Q3W at 20mg/kg. In the dose expansion phase, patients with selected tumor types will be treated with MSB0254 at 16mg/kg Q2W or 20mg/kg Q3W. Primary objectives were to evaluate the safety and tolerability and to identify maximum tolerable dose (MTD) and/or Recommended Phase 2 Dose (RP2D). Secondary objectives included the assessment of pharmacokinetics, immunogenicity, and preliminary efficacy per RECIST1.1. Results: As of 10 th Jan, 2022, a total of 22 Chinese patients have been enrolled into the dose escalation phase and treated with MSB0254 at different dose levels from 4-16mg/kg Q2W or 20mg/kg Q3W. MTD was not reached. One DLT was reported in 12mg/kg Q2W dose cohort. A subject with intra-cholangial carcinoma developed G3 (grade 3) upper gastrointestinal hemorrhage on the C1D13. The adverse event was resolved after symptomatic treatment. The most common treatment-emergent adverse events (TEAEs) (&gt;10%) included: hypertension (27.3%), AST increased (27.3%), γ-GGT increased (22.7%), neutrophil count decreased (18.2%), proteinuria (18.2%), WBC count decreased (13.6%), platelet count decreased (13.6%) and anemia (13.6%). Three subjects (13.6%) experienced G3 TEAEs: 1 upper gastrointestinal hemorrhage, 1 anemia and 1 Hypertriglyceridemia. No G4/5 TEAE was observed. And three subjects (13.6%) experienced 3 SAEs: 1 upper gastrointestinal hemorrhage, 1 G2 intestinal obstruction caused hospitalization and 1 G2 fatigue caused hospitalization. MSB0254 displayed a dose proportional pharmacokinetic profile between 4-16 mg/kg Q2W with calculated T 1/2 of 6-9 days. Eighteen subjects had at least one tumor assessment per RECIST 1.1 after MSB0254 treatment. Eleven subjects (61.1%) had best response of stable disease (SD). Four of them had stable disease for more than 6 months, including a neuroendocrine tumor (NET), a gastric cancer, an epithelioid hemangioendothelioma (EHE) and a submaxillary gland carcinoma patient. Conclusions: MSB0254 demonstrated a manageable safety profile and preliminary antitumor activity in patients with advanced solid tumors. 16mk/kg Q2W is recommended as RP2D. 20mg/kg Q3W is still under investigation. The study of MSB0254 on the expansion phase in selected tumor patients is ongoing. Clinical trial information: NCT04381325.